In immunogenetic and other studies, a need exists for methods for amino acid sequence analysis of proteins that are rapid and sensitive. Techniques involving mass spectrometry (MS) appear to be a promising way for meeting these goals. A dipeptidyl peptidase/gas chromatography-mass spectroscopy (DP/GC-MS) approach has been developed. This method allows polypeptide sequences to be determined from eiter the N- or C-terminus of the polypeptide in nanomolar amounts. The method has been enhanced by the use of computer programs to simplify data handling. Another method for use of MS in these determinations involves direct introduction of suitably modified polypetides of approximately ten residues or less. The DP/GC-MS method is currently being utilized to elucidate the structure of the N-terminal 225 residue fragment resulting from cyanogen bromide cleavage of an a3 allotype homogeneous rabbit IgG heavy chain.